Maternal Broadly Neutralizing Antibodies Select for Neutralization-Resistant Infant Transmitted/Founder HIV Variants

Abstract

Each year, over 180,000 infants become infected via mother-to-child-transmission (MTCT) of HIV despite the wide availability of highly effective maternal antiretroviral treatments, underlining the need for a maternal HIV vaccine to end the pediatric HIV epidemic. Here, we characterized 225 maternal HIV Envelope (Env)-specific IgG monoclonal antibodies (mAbs) from seven U.S. and Malawian HIV-infected non-transmitting and transmitting mothers and examined their neutralization activity against autologous circulating non-transmitted viruses and infant transmitted/founder (T/F) viruses. Maternal linear V3 epitope-specific IgG mAbs neutralized maternal circulating non-transmitted viruses yet their paired infant T/F viruses were neutralization resistant to these V3-specific IgG mAbs. We also report that maternal plasma broadly neutralizing antibody (bNAb) responses targeting the N332 V3 glycan supersite in a transmitting woman selected for an N332 V3 glycan neutralization-resistant infant T/F virus, demonstrating that vertical transmission can occur in the presence of maternal plasma bNAb responses. These data have important implications for vaccination strategies aimed at eliciting bNAbs as well as ongoing clinical trials testing the viral-suppressive or prophylactic-potential of passively administered bNAbs in the setting of MTCT.